Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans

Eligibility Criteria

• 1. Male or female, 18 to 70 years of age, capable of reading and understanding English, and able to provide written informed consent (i.e. no persons who are imprisoned, of minor age, diagnosed with dementia, diagnosed with a terminal illness, or who otherwise require a surrogate to provide informed consent).
• 2. Be on a stable dose of BUP maintenance therapy for at least 7 days at the same maintenance dose. Veterans or non-Veterans who are not currently on a stable dose of BUP maintenance therapy will be referred to the Substance Dependence Treatment Program at the MEDVAMC or the Addiction Clinic at BTGH and invited to screen for this study once BUP treatment is stable.
• 3. Have a positive urine toxicology screen for BUP.
• 4. Has a previous diagnosis of PTSD documented in CPRS or meets criteria for current PTSD as assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).
• 5. Have hematology and chemistry laboratory tests within 3 months of study entry that are within normal (± 15%) limits, except liver function test results, which can be 5X the upper limit of normal.
• 6. Have a medical history and physical examination demonstrating no clinically significant contraindications for study participation within 3 months of study entry.
• 1. DSM-5 criteria for substance use disorders (SUDs) other than OUD, nicotine, or cannabis, or stimulants \[assessed by UDS and the Mini-International Neuropsychiatric Interview (MINI)\].
• 2. Self-reported use of methadone in the last 14 days.
• 3. Be undergoing significant opioid withdrawal, as assessed by the COWS (defined as \>12 on the COWS).
• 4. Increased risk of suicide that necessitates inpatient treatment or warrants therapy excluded by the protocol, and/or current suicidal plan, per investigator clinical judgement, based on interview and defined on the Columbia Suicidality Severity Rating Scale (C-SSRS).
• 5. Females of child-bearing potential must be using medically acceptable birth control (e.g. oral, implantable, injectable, or transdermal contraceptives; intrauterine device; double-barrier method) AND not be pregnant OR have plans for pregnancy or breastfeeding during the study.
• 6. Use of any of the following medications within 30 days prior to enrollment (self-report on Prior/Concomitant Medications (Meds) form):
• 1. Benzodiazepines, barbiturates, or other CNS depressants
• 2. Methadone or any other prescription analgesics, except BUP or BUP/naloxone
• 3. Opioid antagonists such as naltrexone, except naloxone in combination with BUP
• 4. Tricyclic antidepressants, which may reduce the efficacy of imidazoline derivatives
• 5. Drugs that have been associated with QT prolongation, including:
• 1. Fluoroquinolones: ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, etc.
• 2. Macrolides: erythromycin, roxithromycin, azithromycin, clarithromycin, etc.
• 3. Antifungals: ketoconazole, itraconazole, etc. iii. Antipsychotics: haloperidol, thioridazine, ziprasidone, clozapine, quetiapine\*, risperidone\*, olanzapine, etc.
• * The following medications will be permissible at the discretion of the study physician:
• 1. Bupropion a. Allowable dosage of up to 150mg daily (this is well below the therapeutic dose for depression, but is given for smoking cessation)
• 2. Quetiapine
• 3. Risperidone
• 1. Allowable dosage 0.25mg- 1mg daily (below the antipsychotic dose of 2-8 mg daily) Prospective participants must be on a steady dose of the medication to be considered.
• 7. Prescription of any of the following medications within 30 days prior to enrollment (review of EDC patient chart):
• 8. Clinically significant abnormal ECG (such as second- or third-degree heart block, QTc interval ≥500 msec, uncontrolled arrhythmia), and/or history of a myocardial infarction.
• 9. Heart rate \< 55 bpm or symptomatic bradycardia.
• 10. Systolic blood pressure \< 90 mmHg, and/or diastolic blood pressure \< 60 mmHg, and/or symptomatic hypotension.
• 11. Have a history of seizure disorder or severe traumatic brain injury (TBI); per the Ohio State TBI assessment.
• 12. Self-reported HIV/AIDS, active tuberculosis, and/or active syphilis.
• 13. Have significant hepatic, pancreatic (e.g., Type I diabetes), gastrointestinal or renal (that would affect absorption, metabolism or excretion of the study drug), endocrine, cardiac, neurological, psychiatric, pulmonary, hematologic, or other disorders (self-reported during Medical History assessment) that a study clinician believes would make study participation unsafe, treatment compliance difficult, or otherwise be determined by the PI to not be a good study candidate.
• * The following conditions will be permissible at the discretion of the study physician:
• 1. Participants must be receiving MAT for at least 6 months 2. Hemoglobin A1c levels must be stable and relatively low 3 months prior to study entry and at the time of screening ii. Pancreatitis
• 1. There must be 12 months between enrollment and last pancreatitis episode iii. Hepatitis
• 1. Lab work submitted 3 months prior to study entry and at the time of screening should exhibit no elevations in liver functioning tests beyond 3X the upper limit of normal